Potentially dangerous to all mammals and birds, anticoagulant rodenticides are the most frequent cause of poisoning in pets. Pets and wildlife may be poisoned directly from baits or indirectly by consumption of poisoned rodents. Intoxications in domestic animals have resulted from contamination of feed with anticoagulant concentrate, malicious use of these chemicals, and feed mixed in equipment used to prepare rodent bait.
All anticoagulants have the basic coumarin or indanedione nucleus. The “first-generation” anticoagulants (warfarin, pindone, coumafuryl, coumachlor, iso-valeryl indanedione, and others less frequently used) require multiple feedings to result in toxicity. The “intermediate” anticoagulants (chlorophacinone and in particular diphacinone) require fewer feedings than “first-generation” chemicals, and thus are more toxic to nontarget species. The “second-generation” anticoagulants (brodifacoum and bromadiolone) are highly toxic to nontarget species (dogs, cats, and potentially livestock) after a single feeding.
The anticoagulants antagonize vitamin K, which interferes with the normal synthesis of coagulation proteins (factors I, II, VII, IX, and X) in the liver; thus, adequate amounts are not available to convert prothrombin into thrombin. A latent period, dependent on species, dose, and activity, is required, during which clotting factors already present are used up. New products have a longer biologic half-life and therefore prolonged effects (which require prolonged treatment). For example, the half-life in canine plasma of warfarin is 15 hr, diphacinone is 5 days, and bromadiolone is 6 days, with maximum effects estimated at 12–15 days. Brodifacoum may continue to be detectable in serum for up to 24 days.
Clinical signs generally reflect some manifestation of hemorrhage, including anemia, hematomas, melena, hemothorax, hyphema, epistaxis, hemoptysis, and hematuria. Signs dependent on hemorrhage, such as weakness, ataxia, colic, and polypnea, may be seen. Depression and anorexia occur in all species even before bleeding occurs.
Anticoagulant rodenticide toxicosis is usually diagnosed based on history of ingestion of the substance. Differential diagnoses when massive hemorrhage is encountered include disseminated intravascular coagulation, congenital factor deficiencies, von Willebrand's disease, platelet deficiencies, and canine ehrlichiosis. A prolonged prothrombin, partial thromboplastin, or thrombin time in the presence of normal fibrinogen, fibrin degradation products, and platelet counts is strongly suggestive of anticoagulant rodenticide toxicosis, as is a positive therapeutic response to vitamin K1.
Vitamin K1 is antidotal. Recommended dosages vary from 0.25–2.5 mg/kg in warfarin (coumarin) exposure, to 2.5–5 mg/kg in the case of long-acting rodenticide intoxication (diphacinone, brodifacoum, bromadiolone). Vitamin K1 is administered SC (with the smallest possible needle to minimize hemorrhage) in several locations to speed absorption. IV administration of vitamin K1 is contraindicated, as anaphylaxis may occasionally result. The oral form of K1 may be used daily after the first day, commonly at the same level as the loading dose (divided bid). Fresh or frozen plasma (9 mL/kg) or whole blood (20 mL/kg) IV is required to replace needed clotting factors and RBC if bleeding is severe. One week of vitamin K1 treatment is usually sufficient for first-generation anticoagulants. For intermediate and second-generation anticoagulants or if anticoagulant type is unknown, treatment should continue for 2–4 wk to control longterm effects. Administration of oral vitamin K1 with a fat-containing ration, such as canned dog food, increases its bioavailability 4–5 times as compared with vitamin K1 given PO alone.
Coagulation should be monitored weekly until values remain normal for 5–6 days after cessation of therapy. Vitamin K3 given as a feed supplement is ineffective in the treatment of anticoagulant rodenticide toxicosis. Additional supportive therapy may be indicated, including thoracocentesis (to relieve dyspnea due to hemothorax) and supplemental oxygen if needed.
Last full review/revision March 2012 by Frederick W. Oehme, DVM, PhD